Arenavirus family includes a group of bi-segmented enveloped RNA viruses with genomes encoding a total of four genes in opposite orientation (Buchmeier et al., 2007, p. 1791-1827. In Knipe D M, Howley P M (ed.), Fields Virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, Pa.). The Z protein produced from the large (L) genomic segment is a small RING-domain containing matrix protein that mediates virus budding and also regulates viral RNA synthesis. The large L protein (˜200 kDa) encoded also on the L segment is the RNA-dependent RNA polymerase (RdRp) protein that is required for viral RNA synthesis. The glycoprotein (GPC) encoded on the small (S) segment is post-translationally processed into a stable signal peptide (SSP), the receptor-binding G1 protein, and the transmembrane G2 protein. The nucleoprotein (NP) of the S segment encapsidates viral genomic RNAs, is required for viral RNA synthesis, and also suppresses host innate immune responses.
Arenaviruses are zoonotic RNA viruses with rodents as their primary natural hosts (for a review, see McLay et al., 2014, J Gen Virol 95(Pt 1):1-15). Humans can be infected with arenaviruses through direct contact of skin lesions with rodent excretions, eating foods contaminated with rodent excretions, or inhalation of tainted aerosols. Only a few arenaviruses can cause diseases in humans (for a review, see McLay et al., 2013, Antiviral Res 97:81-92). For example, lymphocytic choriomeningitis virus (LCMV) can cause central nerve system diseases, whereas Lassa virus (LASV) and several other arenaviruses can cause hemorrhagic fevers that can potentially result in terminal shock and death. Limited therapeutic options are available for treating these viral infections. The only available antiviral drug (ribavirin) shows some beneficial effects but it has many side effects and must be administered soon after the infection when the disease is often mis-diagnosed as the symptoms are only flu-like and insidious.
Due to the high containment requirement (BSL-4) to work with pathogenic arenaviruses and the cost associated with working with non-human primates, only limited vaccine studies have been done. There are currently no vaccines for these pathogenic arenaviruses, except for the Candid #1 that is not FDA-approved but is available only for off-labeled usage against Junin virus, which causes Argentine hemorrhagic fever. Several safe and convenient systems have been developed to study arenavirus replication and pathogenesis in the conventional BSL-2 laboratory, such as the Pichinde virus model system (Lan et al., 2009, J Virol 83:6357-6362, Liang et al., 2009, Ann NY Acad Sci 1171 Suppl 1:E65-74, Kumar et al., 2012, Virology 433:97-103, Wang et al., 2012, J Virol 86:9794-9801, McLay et al., 2013, J Virol 87:6635-6643). Pichinde virus (PICV) was isolated from rice rats in Columbia. It does not cause disease in humans, but can cause hemorrhagic fever-like symptoms in guinea pigs and thus is an ideal surrogate model to study arenavirus-induced hemorrhagic fevers. Serological evidence suggests a very low seroprevalence in humans (2 out of 82 people living or working in close association with habitats of infected rodents and 6 out of 13 laboratory workers have shown anti-PICV serum positivity but no distinct illnesses (Trapido et al., 1971, Am J Trop Med Hyg 20:631-641, Buchmeier et al., 1974, Infect Immun 9:821-823). Therefore, there is little to no preexisting immunity against PICV in the general human population, in contrast to LCMV, a prototypic arenavirus, which shows 2-5% seroprevalence in humans.